Vashee S, Melcher K, Ding W V, Johnston S A, Kodadek T
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712-1096, USA.
Curr Biol. 1998 Apr 9;8(8):452-8. doi: 10.1016/s0960-9822(98)70179-4.
The promoter regions of most eukaryotic genes contain binding sites for more than one transcriptional activator and these activators often bind cooperatively to promoters. The most common type of cooperativity is supported by direct protein-protein interactions. Recent studies have shown that proteins that do not specifically interact with one another can bind cooperatively to chromatin in vitro. probably by the localized destabilization of nucleosome structure by one factor, facilitating binding of another to a nearby site. This mechanism does not require that the transcription factors have activation domains. We have examined whether this phenomenon occurs in vivo.
Unrelated non-interacting proteins can bind DNA cooperatively in yeast cells; this cooperative binding can contribute significantly to transcriptional activation, does not require that both factors have activation domains and is only operative over relatively short distances. In addition to this 'short-range' mechanism, unrelated non-interacting proteins can bind cooperatively to sites separated by hundreds of base pairs, so long as both have potent activation domains.
Cooperative binding of transcription factors in vivo can occur by several mechanisms, some of which do not require direct protein-protein interactions and which cannot be detected in vitro using naked DNA templates. These findings must be taken into account when evaluating mechanisms for synergistic transcriptional activation.
大多数真核基因的启动子区域包含多个转录激活因子的结合位点，这些激活因子通常协同结合到启动子上。最常见的协同类型是由直接的蛋白质-蛋白质相互作用支持的。最近的研究表明，彼此不发生特异性相互作用的蛋白质在体外可以协同结合到染色质上，这可能是由于一个因子使核小体结构局部不稳定，从而促进另一个因子与附近位点的结合。这种机制并不要求转录因子具有激活结构域。我们研究了这种现象在体内是否发生。
不相关的非相互作用蛋白质可以在酵母细胞中协同结合DNA；这种协同结合对转录激活有显著贡献，不要求两个因子都具有激活结构域，并且仅在相对较短的距离内起作用。除了这种“短程”机制外，不相关的非相互作用蛋白质可以协同结合到相隔数百个碱基对的位点上，只要两者都具有有效的激活结构域。
转录因子在体内的协同结合可以通过多种机制发生，其中一些机制不要求直接的蛋白质-蛋白质相互作用，并且使用裸DNA模板在体外无法检测到。在评估协同转录激活机制时，必须考虑这些发现。
